Chemical diversity and evolution written in the genomes of the Compositae

Chemical diversities in nature are the outcomes of adaptive enzyme evolution over millions of years, and simple synthetic rules of natural products could be imprinted in the genomic lineages of diverse plant species. To understand chemical evolution, we have studied the sesquiterpene lactones (STLs) metabolism in the Compositae family. Compositae is the largest plant family, and it first emerged from South America at about 50 million years ago and has become dominant cosmopolitan plants. One characteristic chemical constituent of Compositae is a sub-class of terpenoids, sesquiterpene lactone (STL). It is believed that thousands of modern STLs have derived from the simple STL, costunolide, and we focused on identifying and characterizing two P450 enzymes [germacrene A oxidase (GAO) and costunolide synthase (COS)] which are required for the costunolide synthesis. GAO catalyzes three-step oxidations of the C12 carbon of sesquiterpene backbone, hence adding a C12 carboxylic acid moiety. Using the public Compositae genomics resources, candidate GAO clones were isolated from a basal lineage (Barnadesioideae) as well as from three major subfamilies of the Compositae. All GAO recombinant enzymes could catalyze the three-step oxidations of native substrate, demonstrating that this activity is conserved at the start of the Compositae evolution. Also, COS was identified from lettuce, and comparative genomics analyses showed that COS is widely conserved in the major subfamilies of Compositae. However, certain tribes lack COS orthologs and instead have evolved homologous enzymes catalyzing distinct regio- and stereo-selective hydroxylation. A conceptual model for STL evolution in the Compositae family will be presented.